NEWPORT, R.I. — Defending champion Ivo Karlovic of Croatia beat American Denis Kudla 6-4, 6-4 on Wednesday in his Hall of Fame Tennis Championships opener to reach the quarterfinals in the grass-court event.

The 38-year-old Karlovic had 16 aces and broke Kudla’s serve three times. Karlovic will face Germany’s Peter Gojowczyk, a 2-6, 6-4, 6-4 winner over Russia’s Konstantin Kravchuk.

Top-seeded John Isner, the big-serving American who won Newport titles in 2011 and 2012, used 13 aces to beat Australia’s Sam Groth 6-2, 6-4. Isner will play fellow American Dennis Novikov, a 6-3, 6-2 winner over Canada’s Frank Dancevic.

American Bjorn Fratangelo also advanced, beating Australia’s Akira Santillan 7-6 (3), 3-6, 6-1.

Two seeded players lost. Tobias Kamke of Germany edged No. 3 Adrian Mannarino, the Frenchman who reached the round of 16 at Wimbledon, 7-6 (5), 7-5, and Australian qualifier Matthew Ebden beat No. 6 Lukas Lacko of Slovakia 6-1, 7-6 (2).

No. 4 Pierre-Hugues Herbert of France’s battled past Spain’s Adrian Menendez-Maceiras 7-5, 2-6, 6-3.